An update on the use of sphingosine 1-phosphate receptor modulators for the treatment of relapsing multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is an immune-mediated disorder of the CNS manifested by recurrent attacks of neurological symptoms (related to focal inflammation) and gradual disability accrual (related to progressive neurodegeneration and neuroinflammation). Sphingosine-1-phosphate-receptor (S1PR) modulators are a class of oral disease-modifying therapies (DMTs) for relapsing MS. The first S1PR modulator developed and approved for MS was fingolimod, followed by siponimod, ozanimod, and ponesimod. All are S1P analogues with different S1PR-subtype selectivity. They restrain the S1P-dependent lymphocyte egress from lymph nodes by binding the lymphocytic S1P-subtype-1-receptor. Depending on their pharmacodynamics and pharmacokinetics, they can also interfere with other biological functions. AREAS COVERED: Our narrative review covers the PubMed English literature on S1PR modulators in MS until August 2022. We discuss their pharmacology, efficacy, safety profile, and risk management recommendations based on the results of phase II and III clinical trials. We briefly address their impact on the risk of infections and vaccines efficacy. EXPERT OPINION: S1PR modulators decrease relapse rate and may modestly delay disease progression in people with relapsing MS. Aside their established benefit, their place and timing within the long-term DMT strategy in MS, as well as their immunological effects in the new and evolving context of the post-COVID-19 pandemic and vaccination campaigns warrant further study.

TNF-α inhibitors used as steroid-sparing maintenance monotherapy in parenchymal CNS sarcoidosis.

OBJECTIVE: To assess the efficacy of tumour necrosis factor-α (TNF-α) inhibitors used as steroid-sparing monotherapy in central nervous system (CNS) parenchymal sarcoidosis. METHODS: The French Multiple Sclerosis and Neuroinflammation Centers retrospectively identified patients with definite or probable CNS sarcoidosis treated with TNF-α inhibitors as steroid-sparing monotherapy. Only patients with CNS parenchymal involvement demonstrated by MRI and imaging follow-up were included. The primary outcome was the minimum dose of steroids reached that was not associated with clinical or imaging worsening during a minimum of 3 months after dosing change. RESULTS: Of the identified 38 patients with CNS sarcoidosis treated with TNF-α inhibitors, 23 fulfilled all criteria (13 females). Treatments were infliximab (n=22) or adalimumab (n=1) for a median (IQR) of 24 (17-40) months. At treatment initiation, the mean (SD) age was 41.5 (10.5) years and median (IQR) disease duration 22 (14-49.5) months. Overall, 60% of patients received other immunosuppressive agents before a TNF-α inhibitor. The mean (SD) minimum dose of steroids was 31.5 (33) mg before TNF-α inhibitor initiation and 6.5 (5.5) mg after (p=0.001). In all, 65% of patients achieved steroids dosing <6 mg/day; 61% showed clinical improvement, 30% stability and 9% disease worsening. Imaging revealed improvement in 74% of patients and stability in 26%. CONCLUSION: TNF-α inhibitors can greatly reduce steroids dosing in patients with CNS parenchymal sarcoidosis, even refractory. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that TNF-α inhibitor used as steroid-sparing monotherapy is effective for patients with CNS parenchymal sarcoidosis.

The future of multiple sclerosis treatments.

INTRODUCTION: There are not many conditions in which the last few decades have brought such a major change in the landscape of treatments as is the case of multiple sclerosis (MS). A number of disease modifying treatments (DMTs) are presently available for the treatment of the inflammatory phase of this disabling disease; however, the need for treating neurodegeneration and halting the progression of disability is still unmet. Areas covered: In this paper we review the available information on existing and emerging DMTs and we discuss their place within the context of different treatment strategies in MS, Expert commentary: The future of MS treatments should include the development of new treatment strategies tackling disease progression, together with a better understanding of the side-effects and the best sequential strategy of implementation of available and emerging drugs.

An Uncommon Cause of Longitudinally Extensive Transverse Myelitis.

Considering that currently Romania has the highest tuberculosis incidence in Europe, the recognition of the infection is an acknowledged health issue. Central nervous system tuberculosis accounts for approximately 1% of all cases of tuberculosis. Longitudinally extensive transverse myelitis is a contiguous infl ammatory lesion of the spinal cord which involves three or more spinal segments. In tuberculosis, spinal cord involvement is rare and is usually rather due to radiculomyelitis or spinal tuberculoma, and only very rare due to longitudinally extensive transverse myelitis. We present the case of a 52-year-old man referred to our department for progressive neurological deficits due to a longitudinally extensive transverse myelitis. After a thorough work-up we diagnosed the patient with longitudinally extensive transverse myelitis secondary to infection with Mycobacterium tuberculosis.

Correlations of Cognitive Impairment with Circadian Blood Pressure Pattern and Intima-Media Thickness in Hypertensive Patients.

INTRODUCTION: Cognitive impairment is strongly associated with arterial hypertension and might be associated also with certain circadian blood pressure patterns. Ambulatory blood pressure monitoring (ABPM) represents a very useful tool in the evaluation of patients with hypertension. Intima-media thickness (IMT), a marker of subclinical organ damage in hypertensive patients is associated with the progression of cognitive impairment. The aim of our study was to correlate the cognitive impairment with the hypertension pattern found with ABPM, IMT, lipid profile and inflammatory syndrome. MATERIALS AND METHODS: We enrolled 40 patients aged between 47 and 88 years (69±11 years) with medical history of essential hypertension and cognitive impairment. All patients underwent neuropsychological examination, ABPM, and B-mode ultrasound of the carotid arteries. RESULTS: 57% of the patients had a nondipping pattern. The blood pressure pattern inversely correlated with the results of MMSE (r=-0.33; p=0.04), patients with nondipping patterns having lower scores than the ones with dipper pattern. Increased IMT was associated with poorer performance on MoCA test (r=-0.33; p=0.005). MoCA and MMSE scores were inversely correlated with the total cholesterol (r=-0.31; p=0.04; and r=0.38; p=0.01 respectively) and with the LDL-cholesterol (r=-0.32; p=0.04; and r=-0.41; p=0.009 respectively). Patients with low scores on MMSE also had high serum levels of C reactive protein (r=-0.33; p=0.045). CONCLUSION: Patients with cognitive impairment and hypertension have vascular changes characterized by increased carotid IMT, alteration of the dipping phenomenon, increased total and LDL-cholesterol, and increased C reactive protein, all related to the degree of cognitive dysfunction.